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1.
Nat Chem ; 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39251841

ABSTRACT

Multi-site functionalization of molecules provides a potent approach to accessing intricate compounds. However, simultaneous functionalization of the reactive site and the inert remote C(sp3)-H poses a formidable challenge, as chemical reactions conventionally occur at the most active site. In addition, achieving precise control over site selectivity for remote C(sp3)-H activation presents an additional hurdle. Here we report an alternative modular method for alkene difunctionalization, encompassing radical-triggered translocation of functional groups and remote C(sp3)-H desaturation via photo/cobalt dual catalysis. By systematically combining radical addition, functional group migration and cobalt-promoted hydrogen atom transfer, we successfully effectuate the translocation of the carbon-carbon double bond and another functional group with precise site selectivity and remarkable E/Z selectivity. This redox-neutral approach shows good compatibility with diverse fluoroalkyl and sulfonyl radical precursors, enabling the migration of benzoyloxy, acetoxy, formyl, cyano and heteroaryl groups. This protocol offers a resolution for the simultaneous transformation of manifold sites.

3.
Sci Total Environ ; 953: 175980, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39236823

ABSTRACT

Assessing the bioaccessibility and bioavailability of cadmium (Cd) is crucial for effective evaluation of the exposure risk associated with intake of Cd-contaminated rice. However, limited studies have investigated the influence of gut microbiota on these two significant factors. In this study, we utilized in vitro gastrointestinal simulators, specifically the RIVM-M (with human gut microbial communities) and the RIVM model (without gut microbial communities), to determine the bioaccessibility of Cd in rice. Additionally, we employed the Caco-2 cell model to assess bioavailability. Our findings provide compelling evidence that gut microbiota significantly reduces Cd bioaccessibility and bioavailability (p<0.05). Notably, strong in vivo-in vitro correlations (IVIVC) were observed between the in vitro bioaccessibilities and bioavailabilities, as compared to the results obtained from an in vivo mouse bioassay (R2 = 0.63-0.65 and 0.45-0.70, respectively). Minerals such as copper (Cu) and iron (Fe) in the food matrix were found to be negatively correlated with Cd bioaccessibility in rice. Furthermore, the results obtained from the toxicokinetic (TK) model revealed that the predicted urinary Cd levels in the Chinese population, based on dietary Cd intake adjusted by in vitro bioaccessibility from the RIVM-M model, were consistent with the actual measured levels (p > 0.05). These results indicated that the RIVM-M model represents a potent approach for measuring Cd bioaccessibility and underscore the crucial role of gut microbiota in the digestion and absorption process of Cd. The implementation of these in vitro methods holds promise for reducing uncertainties in dietary exposure assessment.

4.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 41(4): 790-797, 2024 Aug 25.
Article in Chinese | MEDLINE | ID: mdl-39218606

ABSTRACT

To address the conflict between the "fitness" and "feasibility" of body-fitted stents, this paper investigates the impact of various smoothing design strategies on the mechanical behaviour and apposition performance of stent. Based on the three-dimensional projection method, the projection region was fitted with the least squares method (fitting orders 1-6 corresponded to models 1-6, respectively) to achieve the effect of smoothing the body-fitted stent. The simulation included the crimping and expansion process of six groups of stents in stenotic vessels with different degrees of plaque calcification. Various metrics were analyzed, including bending stiffness, stent ruggedness, area residual stenosis rate, contact area fraction, and contact volume fraction. The study findings showed that the bending stiffness, stent ruggedness, area residual stenosis rate, contact area fraction and contact volume fraction increased with the fitting order's increase. Model 1 had the smallest contact area fraction and contact volume fraction, 77.63% and 83.49% respectively, in the incompletely calcified plaque environment. In the completely calcified plaque environment, these values were 72.86% and 82.21%, respectively. Additionally, it had the worst "fitness". Models 5 and 6 had similar values for stent ruggedness, with 32.15% and 32.38%, respectively, which indicated the worst "feasibility" for fabrication and implantation. Models 2, 3, and 4 had similar area residual stenosis rates in both plaque environments. In conclusion, it is more reasonable to obtain the body-fitted stent by using 2nd to 4th order fitting with the least squares method to the projected region. Among them, the body-fitted stent obtained by the 2nd order fitting performs better in the completely calcified environment.


Subject(s)
Stents , Humans , Prosthesis Design , Computer Simulation , Plaque, Atherosclerotic
5.
World Neurosurg ; 2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39278540

ABSTRACT

PURPOSE: Anterior temporal lobectomy (ATL) is the most common surgical treatment for temporal lobe epilepsy (TLE), and Stereoelectroencephalography (SEEG) plays a critical role in precisely localizing the epileptogenic zone (EZ). This study aimed to explore the effect of SEEG on the long-term outcomes of different side ATL. METHODS: From March 2012 to February 2020, a retrospective analysis was conducted on 231 TLE patients who underwent standard ATL surgery. According to the surgical sides and the utilization of SEEG during preoperative evaluation, the patients were categorized into four groups, with a follow-up period exceeding two years. RESULTS: Among the 231 TLE patients, the probability of being seizure-free two years after the surgery was 80.52%, which decreased to 65.65% after five years. There was no significant difference in outcomes between SEEG and non-SEEG patients. For overall and non-SEEG patients, there was no significant difference in short-term outcomes between different surgical sides. However, the long-term outcomes of right ATL patients were significantly better than left. Interestingly, for patients who underwent SEEG, there was no significant difference in both short-term and long-term outcomes between different surgical sides. CONCLUSION: Some TLE patients encounter challenges in localizing the EZ through non-invasive evaluation, necessitating the use of SEEG for precise localization. Furthermore, their seizure outcomes after surgery can be the same with the patients who have a clear epileptogenic zone in non-invasive evaluation. And SEEG patients can achieve a more stable long-term prognosis than non-SSEEG patients.

6.
PLoS One ; 19(9): e0309723, 2024.
Article in English | MEDLINE | ID: mdl-39269966

ABSTRACT

Agricultural mechanization is a crucial indicator of modernization in agriculture. It improves productivity and underpins the evolution of a modern state. This study scrutinizes the enduring effects of government subsidies on farm machinery acquisition, income growth, and capital accumulation in rural households. It is based on policies about targeted poverty alleviation and rural revitalization. Research findings indicate that government subsidies have significantly increased the per capita net income of rural households. However, in the post-poverty alleviation era, for households that already possess agricultural machinery, the benefits brought by government subsidies in the early stages of the policy cycle tend to diminish over time. From 2016 to 2020, government subsidies continued to enhance the value of agricultural machinery in rural households. Their impact on ownership rates first slightly declined and then increased again. The promotional effect in 2020 was not significantly better than in 2016. When China is fighting against poverty, it is essential to encourage rural households to use their income and government subsidies to accumulate production capital. A long-term mechanism has been established to protect the achievements of poverty alleviation, promote agricultural mechanization and rural modernization, and support rural revitalization.


Subject(s)
Agriculture , Farmers , Income , Poverty , Rural Population , China , Humans , Agriculture/economics , Agriculture/methods , Financing, Government , Family Characteristics
7.
Proc Natl Acad Sci U S A ; 121(37): e2409201121, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39240973

ABSTRACT

Transition metal oxides ion diffusion channels have been developed for ammonium-ion batteries (AIBs). However, the influence of microstructural features of diffusion channels on the storage and diffusion behavior of NH4+ is not fully unveiled. In this study, by using MnCo2O4 spinel as a model electrode, the asymmetric ion diffusion channels of MnCo2O4 have been regulated through bond length optimization strategy and investigate the effect of channel size on the diffusion process of NH4+. In addition, the reducing channel size significantly decreases NH4+ adsorption energy, thereby accelerating hydrogen bond formation/fracture kinetics and NH4+ reversible diffusion within 3D asymmetric channels. The optimized MnCo2O4 with oxygen vacancies/carbon nanotubes composite exhibits impressive specific capacity (219.2 mAh g-1 at 0.1 A g-1) and long-cycle stability. The full cell with 3,4,9,10-perylenetetracarboxylic diimide anode demonstrates a remarkable energy density of 52.3 Wh kg-1 and maintains 91.9% capacity after 500 cycles. This finding provides a unique approach for the development of cathode materials in AIBs.

8.
ACS Sens ; 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39283684

ABSTRACT

Natural products play a significant role in new drug discovery and anticancer therapy, making the evaluation of their anticancer efficiency crucial for clinical application. However, delivering natural products to single cells and in situ monitoring of induced signaling molecule fluctuation to evaluate anticancer efficiency remain significant challenges. Hence, we proposed a universal and straightforward strategy to construct a bifunctional nanoelectrode that integrates drug loading and monitoring of signal molecule fluctuations at the single-cell level. Platinum (Pt) nanoparticles/reduced graphene oxide (rGO) composites were first electrochemically deposited on the carbon fiber nanoelectrode (CFNE@Pt/rGO) to serve as electrocatalytic materials for the monitoring of natural-product-induced reactive oxygen species (ROS) generation. The GO/natural product complex, formed by π-π stacking and hydrophobic interactions, was further electrochemically reduced on the surface of CFNE@Pt/rGO to enable the CFNE drug-loading function. Using this bifunctional functional nanoelectrode, a series of natural products (such as capsaicin, curcumin, and chrysin) were delivered into single cancer cells, and their anticancer efficiency was evaluated by measuring ROS generation. The results showed that intracellular ROS production induced by chrysin was 1.5-fold greater than that of curcumin and 2.1-fold greater than that of capsaicin. This work proposes an effective tool to evaluate the anticancer efficiency of various natural products. Additionally, this nanotool can be expanded to monitor the fluctuation of other biomolecules (such as RNS, GSH, NADH, etc.) by replacing Pt nanoparticles with other electrocatalytic materials, which is significant for comprehensively exploring the anticancer efficiency of new drugs and for the clinical treatment of various diseases.

9.
Microbiol Spectr ; : e0061124, 2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39292002

ABSTRACT

This study explores the effects of disinfectant and antibiotic exposure on gut health, focusing on gut microbiota balance and gut immune function. Our analysis indicates that disinfectants increase the proportion of Gram-positive bacteria, particularly increasing Staphylococcus levels, while antibiotics increase the proportion of Gram-negative bacteria, especially Bacteroides levels. These changes disrupt microbial harmony and affect the gut microbiome's functional capacity. Additionally, our research reveals that both disinfectants and antibiotics reduce colon length and cause mucosal damage. A significant finding is the downregulation of NLRC4, a key immune system regulator in the gut, accompanied by changes in immune factor expression. This interaction between chemical exposure and immune system dysfunction increases susceptibility to inflammatory bowel disease and other gut conditions. Given the importance of disinfectants in disease prevention, this study advocates for a balanced approach to their use, aiming to protect public health while minimizing adverse effects on the gut microbiome and immune function. IMPORTANCE: Disinfectants are extensively employed across various sectors, such as the food sector. Disinfectants are widely used in various sectors, including the food processing industry, animal husbandry, households, and pharmaceuticals. Their extensive application risks environmental contamination, impacting water and soil quality. However, the effect of disinfectant exposure on the gut microbiome and the immune function of animals remains a significant, unresolved issue with profound public health implications. This highlights the need for increased scrutiny and more regulated use of disinfectants to mitigate unintended consequences on gut health and maintain immune system integrity.

10.
Plant Dis ; 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39238251

ABSTRACT

Amorphophallus konjac, commonly called voodoo lily, is a cash crop widely cultivated in southwest China (Gao et al. 2022). In August 2022, leaf spot symptoms were observed in a field (1 ha) located at Fuyuan (25.67°N; 104.25°E), Yunnan, China, resulting in substantial economic losses. Brown lesions, with an incidence ranging from 20 to 40%, typically had a whitish or gray center and were surrounded by yellow halos. Microscopic observations of the spots revealed anamorphic species Cercospora chevalieri. Conidiophores were 50-150 × 4-7 µm, cylindrical, unbranched, smooth-walled, pale brown and aggregated in dense fascicles arising from a brown stroma. The conidiogenous cells were integrated, terminal or intercalary, pale brown to brown and proliferated sympodially. The conidiogenous loci were thickened and darkened, and 2-3 µm in diam. The conidia were formed singly, obclavate-cylindrical, 90-160 × 5-7 µm, with an average of 130 × 6 µm (n = 30), 6-11 septa, thin-walled, smooth, hyaline or subhyaline, straight or curved with an obtuse apex and obconically truncate base, with thickened and darkened hilum. These morphological characteristics matched those of C. chevalieri, the causal agent of leaf spot on A. paeoniifolius (Braun et al. 2014; Saccardo et al. 1913). A conidial suspension in sterile water from lesions was used to inoculate water agar, and germinated conidia were transferred to potato dextrose agar(PDA) and incubated at 27°C for 7 days. Induction of sporulation was unsuccessful using PDA, as well as malt extract agar, potato sucrose agar and synthetic nutrient-poor agar. Two out of ten isolates were selected for molecular identification and pathogenicity assay. Genomic DNA from two pure isolates (KUNCC22-12536 and KUNCC22-12537) was extracted for PCR and amplified with primers for the internal transcribed spacers (ITS: ITS1/ITS4), calmodulin (CMD: CAL228F/CAL2Rd), translation elongation factor 1-alpha (TEF1-α: 728F/986R), actin (ACT: 512F/783R), histone H3 (HIS3: CYLH3F/CYLH3R), beta-tubulin gene (TUB2: BT-1F/BT-1R) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH: Gpd1/Gpd2), respectively (Vaghefi et al. 2021). The newly generated sequences for ITS (OP719153/OP719154), CMD(OP740904/OP740905), TEF1-α (OP740910/OP740911), ACT (OP740902/OP740903), HIS3 (OP740908/OP740909), TUB2 (OP740912/OP740913), GAPDH (OP740906/OP740907) of C. chevalieri were submitted to GenBank. So far, no sequence data of C. chevalieri were available in the GenBank database. As expected, most genes (TEF1-α, ACT, CMD, HIS, TUB2 and GAPDH) showed 91 to 95% identity to their best hits within species of the genus Cercospora. The phylogenetic tree showed that sequences retrieved from two isolates obtained from the A. konjac leaf spots clustered together within Cercospora forming a strongly supported clade. To test Koch's postulates, ten four-month-old healthy A. konjac plants grown in pots were used for a pathogenicity test in a greenhouse. One leaf of each plant was inoculated with mycelial plugs, and one leaf was inoculated with a sterile PDA plug. These plants were enclosed in plastic bags for 72 h. Only leaves inoculated with mycelium plugs produced brown lesions, which appeared after 10 to 14 days on inoculated leaves. Control plants treated with sterile PDA plugs remained asymptomatic. This experiment was repeated twice with the same results. C. chevalieri was reisolated from infected leaves and identified based on morphology and Sanger sequencing of the ITS region. To our knowledge, this is the first report of C. chevalieri causing leaf spot on A. konjac and the first report of this species from China (Braun et al. 2014), which provides key information for diagnosis and management of this disease.

11.
Int Immunopharmacol ; 142(Pt A): 113034, 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39226826

ABSTRACT

Breast cancer remains one of the primary causes of cancer-related death. An imbalance of oestrogen homeostasis and an inflammatory tumor microenvironment (TME) are vital risk factors for the progression and metastasis of breast cancer. Here, we showed that oestrogen homeostasis was disrupted both in breast cancer patients and in a transgenic MMTV-PyMT mouse model of breast cancer, and significant levels of hydroxylated oestrogen accumulated in the mammary tissues of these patients and mice. We also observed that tumor-associated macrophages (TAMs) were the main population of immune cells present in the breast TME. TAM-dependent tumor metastasis could be triggered by hydroxylated oestrogen via NLRP3 inflammasome activation and IL-1ß production. Mechanistically, TAM-derived inflammatory cytokines induced the expression of matrix metalloproteinases (MMPs) in breast tumor cells, leading to breast tumor invasion and metastasis. Conceptually, our study reveals a previously unknown role of hydroxylated oestrogen in the reprogramming of the TME via NLRP3 inflammasome activation in TAMs, which ultimately facilitates breast cancer cells proliferation, migration, and invasion.

12.
Int J Nanomedicine ; 19: 9145-9160, 2024.
Article in English | MEDLINE | ID: mdl-39258005

ABSTRACT

Background: Triple negative breast cancer (TNBC) is one of the worst prognosis types of breast cancer that urgently needs effective therapy methods. However, cancer is a complicated disease that usually requires multiple treatment modalities. Methods: A tumor microenvironment (TME)-responsive PFC/TRIM37@Fe-TA@HA (abbreviated as PTFTH) nanoplatform was constructed by coating Fe3+ and tannic acid (TA) on the surface of TRIM37-siRNA loaded phase-transition perfluorocarbon (PFC) nanodroplets and further modifying them with hyaluronic acid (HA) to achieve tumor-specific mild photothermal/gene/ferroptosis synergistic therapy (MPTT/GT/ Ferroptosis) in vitro. Once internalized into tumor cells through CD44 receptor-mediated active targeting, the HA shell of PTFTH would be preliminarily disassembled by hyaluronidase (HAase) to expose the Fe-TA metal-phenolic networks (MPNs), which would further degrade in response to an acidic lysosomal environment, leading to HAase/pH dual-responsive release of Fe3+ and PFC/TRIM37. Results: PTFTH showed good biocompatibility in vitro. On the one hand, the released Fe3+ could deplete the overexpressed glutathione (GSH) through redox reactions and produce Fe2+, which in turn converts endogenous H2O2 into highly cytotoxic hydroxyl radicals (•OH) for chemodynamic therapy (CDT). On the other hand, the local hyperthermia generated by PTFTH under 808 nm laser irradiation could not only improve CDT efficacy through accelerating the Fe2+-mediated Fenton reaction, but also enhance TRIM37-siRNA delivery for gene therapy (GT). The consumption of GSH and accumulation of •OH synergistically augmented intracellular oxidative stress, resulting in substantial tumor cell ferroptosis. Moreover, PTFTH possessed outstanding contrast enhanced ultrasound (CEUS), photoacoustic imaging (PAI) and magnetic resonance imaging (MRI) ability. Conclusion: This PTFTH based multiple-mode therapeutic strategy has successfully achieved a synergistic anticancer effect in vitro and has the potential to be translated into clinical application for tumor therapy in future.


Subject(s)
Ferroptosis , Glutathione , Hyaluronic Acid , Nanoparticles , Photothermal Therapy , RNA, Small Interfering , Tannins , Triple Negative Breast Neoplasms , Tumor Microenvironment , Humans , Ferroptosis/drug effects , Glutathione/metabolism , Glutathione/chemistry , Tumor Microenvironment/drug effects , Cell Line, Tumor , Tannins/chemistry , Tannins/pharmacology , Nanoparticles/chemistry , Hyaluronic Acid/chemistry , Female , Triple Negative Breast Neoplasms/therapy , Triple Negative Breast Neoplasms/genetics , RNA, Small Interfering/chemistry , RNA, Small Interfering/pharmacology , RNA, Small Interfering/genetics , Photothermal Therapy/methods , Fluorocarbons/chemistry , Fluorocarbons/pharmacology , Tripartite Motif Proteins/genetics , Tripartite Motif Proteins/metabolism , Genetic Therapy/methods , Combined Modality Therapy/methods , Animals , Iron/chemistry , Hyaluronoglucosaminidase/genetics , Hyaluronoglucosaminidase/metabolism
13.
ACS Nano ; 2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39294859

ABSTRACT

A dynamic-regulated Pd-Fe-N electrocatalyst was effectively constructed with electron-donating and back-donating effects, which serves as an efficient engineering strategy to optimize the electrocatalytic activity. The designed PdFe3/FeN features a comprehensive electrocatalytic performance toward the nitrogen reduction reaction (NRR, yield rate of 29.94 µg h-1 mgcat-1 and FE of 38.43% at -0.2 V vs RHE) and oxygen evolution reaction (OER, 308 mV at 100 mA cm-2). Combining in situ ATR-FTIR, XAS, and DFT results, the role of the interstitial-N-dopant-induced electron sponge effect has been significantly elucidated in strengthening the electrocatalytic NRR process. Specifically, the introduction of a N dopant, an electron acceptor, initiates the generation of robust Lewis-acidic Fe sites, facilitating free N2 capture and bonding. Simultaneously, after NH3 adsorption, the N dopant can back-donate electrons to Fe sites, strengthening the NH3 deportation through weakening the Lewis acidity of Fe centers. Besides, the electron-deficient Fe sites contribute to the reconstruction of FeOOH, the real active species during the OER, which accelerates the four-electron reaction kinetics. This research offers a perspective on electrocatalyst design, potentially facilitating the evolution of advanced material engineering for efficient electrocatalytic synthesis and energy storage.

14.
Plant Genome ; : e20512, 2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39295194

ABSTRACT

Wheat (Triticum aestivum L.) production must be doubled in the next 25 years to meet the global food demand. Harvest index (HI) is an important indicator of efficient partitioning of photosynthetic assimilates to grains. Reducing competition from alternative sinks, such as stems, and deviating assimilates toward grain increase grain number (GN), HI, and grain yield (GY). Novel partitioning traits have great potential to be utilized in wheat breeding programs to increase HI. In this study, we evaluated 236 US facultative soft wheat genotypes for multiple stem and spike partitioning traits at 7 days after anthesis, and for GN, HI, and GY in two locations of Florida in 2016-2017 and 2017-2018 wheat growing seasons. The panel was genotyped with 20,706 single nucleotide polymorphisms generated by genotype-by-sequencing approach. Spike partitioning index (SPI) showed negative significant correlations with lamina partitioning index and true stem partitioning index. Internode 2 and 3 lengths and partitioning indices had significant negative correlations with SPI and HI. The results indicate enhanced competition for assimilates between spikes and second and third internodes during stem elongation. Genome-wide association study (GWAS) identified 114 unique significant marker-trait associations (MTAs) for 12 traits, and 58 MTAs were found within genes that encode different proteins related to biotic/abiotic stress tolerance and other functions. Significant MTAs identified in the GWAS were converted into kompetitive allele specific PCR markers. Some of the markers were validated and can be effectively employed in marker-assisted selection to improve HI, GY, and GN.

15.
CNS Neurosci Ther ; 30(8): e14911, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39145422

ABSTRACT

BACKGROUND: Epilepsy is a widespread central nervous system disorder with an estimated 50 million people affected globally. It is characterized by a bimodal incidence peak among infants and the elderly and is influenced by a variety of risk factors, including a significant genetic component. Despite the use of anti-epileptic drugs (AEDs), drug-refractory epilepsy develops in about one-third of patients, highlighting the need for alternative therapeutic approaches. AIMS: The primary aim of this study was to evaluate the neuroprotective effects of troglitazone (TGZ) in epilepsy and to explore the potential mechanisms underlying its action. METHODS: We employed both in vitro and in vivo models to assess TGZ's effects. The in vitro model involved glutamate-induced toxicity in HT22 mouse hippocampal neurons, while the in vivo model used kainic acid (KA) to induce epilepsy in mice. A range of methods, including Hoechst/PI staining, CCK-8 assay, flow cytometry, RT-PCR analysis, Nissl staining, scanning electron microscopy, and RNA sequencing, were utilized to assess various parameters such as cellular damage, viability, lipid-ROS levels, mitochondrial membrane potential, mRNA expression, seizure grade, and mitochondrial morphology. RESULTS: Our results indicate that TGZ, at doses of 5 or 20 mg/kg/day, significantly reduces KA-induced seizures and neuronal damage in mice by inhibiting the process of ferroptosis. Furthermore, TGZ was found to prevent changes in mitochondrial morphology. In the glutamate-induced HT22 cell damage model, 2.5 µM TGZ effectively suppressed neuronal ferroptosis, as shown by a reduction in lipid-ROS accumulation, a decrease in mitochondrial membrane potential, and an increase in PTGS2 expression. The anti-ferroptotic effect of TGZ was confirmed in an erastin-induced HT22 cell damage model as well. Additionally, TGZ reversed the upregulation of Plaur expression in HT22 cells treated with glutamate or erastin. The downregulation of Plaur expression was found to alleviate seizures and reduce neuronal damage in the mouse hippocampus. CONCLUSION: This study demonstrates that troglitazone has significant therapeutic potential in the treatment of epilepsy by reducing epileptic seizures and the associated brain damage through the inhibition of neuronal ferroptosis. The downregulation of Plaur expression plays a crucial role in TGZ's anti-ferroptotic effect, offering a promising avenue for the development of new epilepsy treatments.


Subject(s)
Epilepsy , Ferroptosis , Neuroprotective Agents , Troglitazone , Animals , Mice , Epilepsy/drug therapy , Epilepsy/chemically induced , Ferroptosis/drug effects , Ferroptosis/physiology , Neuroprotective Agents/pharmacology , Neurons/drug effects , Neurons/metabolism , Hippocampus/drug effects , Hippocampus/pathology , Hippocampus/metabolism , Glutamic Acid/metabolism , Male , Kainic Acid/toxicity , Mice, Inbred C57BL , Membrane Potential, Mitochondrial/drug effects , Anticonvulsants/pharmacology , Anticonvulsants/therapeutic use
16.
Plant J ; 2024 Aug 22.
Article in English | MEDLINE | ID: mdl-39172024

ABSTRACT

Cotton fiber (Gossypium hirsutum) serves as an ideal model for investigating the molecular mechanisms of plant cell elongation at the single-cell level. Brassinosteroids (BRs) play a crucial role in regulating plant growth and development. However, the mechanism by which BR influences cotton fiber elongation remains incompletely understood. In this study, we identified EXORDIUM-like (GhEXL3) through transcriptome analysis of fibers from BR-deficient cotton mutant pagoda 1 (pag1) and BRI1-EMS-SUPPRESSOR 1 (GhBES1.4, encoding a central transcription factor of BR signaling) overexpression cotton lines. Knockout of GhEXL3 using CRISPR/Cas9 was found to impede cotton fiber elongation, while its overexpression promoted fiber elongation, suggesting a positive regulatory function for GhEXL3 in fiber elongation. Furthermore, in vitro ovule culture experiments revealed that the overexpression of GhEXL3 partially counteracted the inhibitory effects of brassinazole (BRZ) on cotton fiber elongation, providing additional evidence of GhEXL3 involvement in BR signaling pathways. Moreover, our findings demonstrate that GhBES1.4 directly binds to the E-box (CACGTG) motif in the GhEXL3 promoter region and enhances its transcription. RNA-seq analysis revealed that overexpression of GhEXL3 upregulated the expression of EXPs, XTHs, and other genes associated with fiber cell elongation. Overall, our study contributes to understanding the mechanism by which BR regulates the elongation of cotton fibers through the direct modulation of GhEXL3 expression by GhBES1.4.

17.
Int J Dermatol ; 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39090834

ABSTRACT

Subcutaneous granuloma annulare (SGA) is a rare clinicopathologic subtype of granuloma annulare characterized by the presence of subcutaneous nodules. There are no present reviews synthesizing the clinical features and treatment modalities in SGA. We conducted a systematic review following PRISMA guidelines [CRD42022344672] on all peer-reviewed English-language studies that reported one or more cases of SGA. A total of 97 studies, comprising 26 case series and 71 case reports with 324 patients, were included for analysis. Most cases were predominantly pediatric, with 78.9% of the cases identified being age 16 or lower and a median age of diagnosis of 6. There was no overall gender predisposition. Although over two-thirds of patients did not have any comorbidities, diabetes mellitus was the most common comorbidity present in 4% of cases. The most common feature of SGA was nodules, which were present in 99.6% of patients. Pain or tenderness was reported in 15.4%, and erythema of overlying skin in 11.0% of cases. Surgical excision was performed in 96/141 (68.1%) patients. Among the 27/141 (18.0%) patients who were conservatively managed, 87.0% spontaneously improved, including 60.0% who completely self-resolved. Topical and intralesional steroids were used in 3.40% and 1.85% of patients, respectively, resulting in complete or partial resolution in 54.6% and 100%. Among patients who were followed up, 83/324 (25.6%) patients experienced recurrence after a median duration of 26 weeks. SGA is predominantly a pediatric disease that frequently occurs on the limbs and the head. Juxta-articular lesions are more commonly observed in adults than in children. Surgical excision is common and effective in most patients. Spontaneous improvement occurs in most untreated cases, and intralesional steroids but not topical steroids may be beneficial for non-resolving cases and to reduce time to resolution.

18.
Ecol Evol ; 14(8): e70159, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39193169

ABSTRACT

The evolutionary patterns of the mitochondrial genome are influenced by both adaptive and nonadaptive forces, with their contributions varying among taxa. There appears to be a correlation linking mutagenesis and latitude, which could be due to differences in metabolic rates. These discrepancies in metabolic rates exhibit a positive connection with mutation pressure. On this basis, we hypothesise that nonadaptive forces play a role in the differences in mutation rates observed along latitudinal gradients. In this study, we selected widely distributed carnivores as representatives of mammals to test our hypothesis. We examined the correlations between the dN/dS ratio (ω), as well as the substitution rates (dS and dN), of 13 PCGs in the mtDNA of 122 carnivores, and the latitude and climatic factors. We found that taxa distributed in higher latitudes tend to have higher substitution rates, but not ω values indicating selective pressure. Notably, dN shows a strong positive correlation with dS, although dS is primarily influenced by mutation pressure, while dN is also influenced by effective population size (N e ). Phylogenetic generalised least squares (PGLS) regression analyses showed that both substitution rates were correlated with climatic factors representing the temperature, precipitation and variability of climate. Based on our findings, we propose that the mutations are primarily influenced by nonadaptive forces (mutation pressure). This forms the fundamental premise for natural selection and speciation. Moreover, the correlation between substitution rates and latitudinal distribution and climate, which are outcomes of nonadaptive factors, can aid in comprehending the global distribution of species diversity.

19.
Vet Microbiol ; 297: 110216, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39151256

ABSTRACT

Pseudorabies virus (PRV), an α-herpesvirus, induces immunosuppression and can lead to severe neurological diseases. N-methyl-D-aspartate receptor (NMDAR), an important excitatory nerve receptor in the central nervous system, is linked to various nervous system pathologies. The link between NMDAR and PRV-induced neurological diseases has not been studied. In vivo studies revealed that PRV infection triggers a reduction in hippocampal NMDAR expression, mediated by inflammatory processes. Extensive hippocampal neuronal degeneration was found in mice on the 6th day by hematoxylin-eosin staining, which was strongly correlated with increased NMDAR protein expression. In vitro studies utilizing the CCK-8 assay demonstrated that treatment with an NMDAR antagonist significantly heightened the cytotoxic effects of PRV on T lymphocytes. Notably, NMDAR inhibition did not affect the replication ability of PRV. However, it facilitated the accumulation of pro-inflammatory cytokines in PRV-infected T cells and enhanced the transcription of the CD25 gene through the secretion of interleukin-2 (IL-2), consequently exacerbating immunosuppression. In this study, we found that NMDAR has functional activity in T lymphocytes and is crucial for the inflammatory and immune responses triggered by PRV infection. These discoveries highlight the significant role of NMDAR in PRV-induced neurological disease pathogenesis.


Subject(s)
Herpesvirus 1, Suid , Pseudorabies , Receptors, N-Methyl-D-Aspartate , Animals , Mice , Herpesvirus 1, Suid/immunology , Receptors, N-Methyl-D-Aspartate/immunology , Receptors, N-Methyl-D-Aspartate/metabolism , Pseudorabies/virology , Pseudorabies/immunology , T-Lymphocytes/immunology , T-Lymphocytes/virology , Hippocampus/virology , Hippocampus/immunology , Cytokines/metabolism , Cytokines/immunology , Cytokines/genetics , Immunosuppression Therapy , Immune Tolerance , Interleukin-2 Receptor alpha Subunit/genetics , Interleukin-2 Receptor alpha Subunit/immunology , Interleukin-2/immunology , Interleukin-2/genetics
20.
Small ; : e2405865, 2024 Aug 24.
Article in English | MEDLINE | ID: mdl-39180457

ABSTRACT

The introduction of noble metal into spinel structure is an effective strategy to develop efficient oxygen evolution/reduction reaction (OER/ORR) catalysts. Herein, surface Cooct is substituted by Ruoct in Rux-Mn0.5Co2.5-xO4/NCNTs by ion-exchange, where presence of Ruoct─O─Cooct unit facilitates electron transfer. This strong electron coupling effect leads downward shift in d-band center and a narrowing of d-p bandgap. The increased charge density of Cooct bridged with Ruoct dioxygen optimizes adsorption of oxygen intermediates (*OH) and occupation of electrons in eg-orbital octahedral. The measured ORR/OER voltage difference is only 0.71 V. The peak power density of assembled zinc-air battery reaches 148.8 mW h cm-2, and energy density at 100 mA cm-2 reaches 813.6 mA h gZn -1, approaching a theoretical value of 820 mA h gZn -1. The catalyst demonstrates stable operation for over 500 h at 10 mA cm-2 and over 200 h at 50 mA cm-2. This work provides new insights to guide fabrication of advanced oxygen electrocatalysts.

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